Vitamin B6 activity is found in three related, naturally occurring compounds: Pyridoxine, Pyridoxal ,and Pyridoxamine. For the sake of convenience, they are all grouped under the heading pyridoxine. Nutritional Pathology Online : click

These compounds are widely distributed in vegetable and animal foods.

Pyridoxine is converted to pyridoxal phosphate, a coenzyme for many enzymes, including transaminases and carboxylases. Vitamins : click

Pyridoxine deficiency is rarely caused by an inadequate diet, although infants who have been fed a poorly prepared powdered formula in which the pyridoxine has been destroyed during preparation have suffered convulsions.

A higher demand for the vitamin, such as may occur in pregnancy, may lead to a secondary deficiency state.

Of particular concern is the deficiency of pyridoxine that follows prolonged medication with a number of drugs, particularly isoniazid, cycloserine, and penicillamine.

A deficiency state is also occasionally seen in alcoholics.

There are no clinical manifestations of the disease that can be considered characteristic or pathognomonic.

The usual dermatologic complications of other B vitamin deficiencies are seen with pyridoxine deficiency.

The primary expression of the disease is in the central nervous system, a feature consistent with the role of this vitamin in the formation of pyridoxal-dependent decarboxylase of the neurotransmitter gamma aminobutyric acid (GABA).

In infants and children, diarrhea, anemia, and seizures have occurred.

Conditions are encountered in which there is no clinical or biochemical evidence of pyridoxine deficiency, yet large doses of the vitamin are useful in treating the disorder.

Such diseases are termed pyridoxine-dependency syndromes, and include anemia, convulsions, and homocystinuria caused by cystathionine synthetase deficiency.

Pyridoxine-responsive anemia is hypochromic and microcytic, and therefore can be confused with the iron deficiency anemia.

Unlike iron-deficiency anemia, however, pyridoxine-responsive anemia is characterized by saturation of iron stores and an increased saturation of transferrin.

Thus, administration of iron may simply make pyridoxine-responsive anemia worse.

By definition, the anemia responds well to massive doses of pyridoxine.

It has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population - impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer.

Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

Association of common variable immunodeficiency with vitamin B(6) deficiency.Eur J Clin Nutr. 2007 Feb 21;

Objective:To study the prevalence of vitamin B(6) deficiency in common variable immunodeficiency and the impact of vitamin B(6) supplementation on immune function in the disorder.Design:Open, non-blinded.Setting:Medical School Hannover, Hannover, Germany.Subjects:Plasma vitamin B(6) concentrations were measured in all the 54 common variable immunodeficiency (CVID) patients visiting our outpatients' clinics in 2005.Interventions:The 17 patients with a decreased vitamin B(6) concentration were recommended to take 50 mg of vitamin B(6)/day for 3 months. Then, vitamin B(6) concentrations, absolute number of lymphocyte populations and immunoglobulin concentrations were controlled.Results:Vitamin B(6) concentrations were reduced in 17/54 patients. All 11/17 patients following our advice to substitute vitamin B(6) had normal vitamin B(6) plasma concentrations 3 months later. In parallel, the number of CD4(+) T cells significantly increased. In contrast, concentrations of serum immunoglobulins were not improved.Conclusions:Vitamin B(6) deficiency is common in CVID. The vitamin deficiency is not the cause of CVID and vitamin supplementation does not relieve humoral immunodeficiency. Nevertheless, vitamin B(6) should be measured in CVID to avoid possible long-term complications of its deficiency.

Vitamin B6 status, deficiency and its consequences--an overview.Nutr Hosp. 2007 Jan-Feb;22(1):7-24.

BACKGROUND: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly. OBJECTIVE: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. RESULTS AND CONCLUSION: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

Low pyridoxal 5'-phosphate is associated with increased risk of coronary artery disease. Nutrition. 2006 Nov-Dec;22(11-12):1146-51. Epub 2006 Oct 10.

OBJECTIVE: The purpose of this study was to investigate the association between plasma pyridoxal 5'-phosphate (PLP) status and lipid profiles and to estimate the relation to the risk of coronary artery disease (CAD). METHODS: Patients who were identified by cardiac catheterization as having > or =70% stenosis of one major coronary artery were assigned to the case group (n = 184). The control group (n = 516) was comprised of healthy individuals with normal blood biochemical values. Plasma PLP, homocysteine, high-sensitivity C-reactive protein, lipid profiles (total cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triacylglycerol) were determined. RESULTS: Subjects with a plasma PLP level <30 nmol/L exhibited a significantly increased risk of CAD compared with subjects with a plasma PLP level > or =30 nmol/L (odds ratio, 1.85; 95% confidence interval, 1.16-2.95) after adjusting for homocysteine and high-sensitivity C-reactive protein. The association between PLP and the risk of CAD remained significant after each lipid profile was additionally adjusted. In addition, the combined presence of low PLP level and an abnormal lipid level increased the risk of CAD to an even greater degree. CONCLUSIONS: A borderline vitamin B6 deficiency (plasma PLP concentration <30 nmol/L) is strongly associated with the risk of CAD. The combined presence of low PLP and abnormal lipid levels increased the risk of CAD even further.

B6-responsive disorders: a model of vitamin dependency.J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):317-26.

Pyridoxal phosphate is the cofactor for over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction, particularly epilepsy. There are several different mechanisms that lead to an increased requirement for pyridoxine and/or pyridoxal phosphate. These include: (i) inborn errors affecting the pathways of B(6) vitamer metabolism; (ii) inborn errors that lead to accumulation of small molecules that react with pyridoxal phosphate and inactivate it; (iii) drugs that react with pyridoxal phosphate; (iv) coeliac disease, which is thought to lead to malabsorption of B(6) vitamers; (v) renal dialysis, which leads to increased losses of B(6) vitamers from the circulation; (vi) drugs that affect the metabolism of B(6) vitamers; and (vii) inborn errors affecting specific pyridoxal phosphate-dependent enzymes. The last show a very variable degree of pyridoxine responsiveness, from 90% in X-linked sideroblastic anaemia (delta-aminolevulinate synthase deficiency) through 50% in homocystinuria (cystathionine beta-synthase deficiency) to 5% in ornithinaemia with gyrate atrophy (ornithine delta-aminotransferase deficiency). The possible role of pyridoxal phosphate as a chaperone during folding of nascent enzymes is discussed. High-dose pyridoxine or pyridoxal phosphate may have deleterious side-effects (particularly peripheral neuropathy with pyridoxine) and this must be considered in treatment regimes. None the less, in some patients, particularly infants with intractable epilepsy, treatment with pyridoxine or pyridoxal phosphate can be life-saving, and in other infants with inborn errors of metabolism B(6) treatment can be extremely beneficial.

Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment.Curr Opin Neurol. 2006 Apr;19(2):148-53.

PURPOSE OF REVIEW: Pyridoxine dependency is an uncommon but important cause of intractable seizures presenting in infancy and early childhood. This paper discusses recent clinical, biochemical and genetic studies and how the findings should change our approach in evaluating young patients with antiepileptic drug-resistant seizures. RECENT FINDINGS: Originally thought to be due to abnormal binding of pyridoxal phosphate to glutamic acid decarboxylase resulting in decreased gamma-aminobutyric acid, mutations in the gene encoding this enzyme have been ruled out. While linkage to 5q31 has been demonstrated, a disease-causing gene in that region has not been identified. Further haplotype analysis of six affected kindreds has demonstrated genetic heterogeneity for this rare disorder. Other studies demonstrate that some children with intractable seizures respond to pyridoxal phosphate rather than pyridoxine, including a rare form of neonatal epileptic encephalopathy shown to be due to mutations in the PNPO gene for pyridox(am)ine 5'-phosphate oxidase. While the biochemical explanation for this finding is not clear, elevated pipecolic acid levels may serve as a diagnostic marker for patients with pyridoxine-dependent seizures. SUMMARY: The results of these studies should prompt clinicians to adopt new strategies for diagnosis and therapy for young patients with intractable seizures. Levels of both pipecolic acid and certain metabolites shown to be elevated in patients with PNPO mutations should be measured, and therapeutic trials of pyridoxal phosphate as well as pyridoxine should be considered early in the course of the management of infants and young children with intractable seizures.

Inflammation causes tissue-specific depletion of vitamin B6.Arthritis Res Ther. 2005;7(6):R1254-62.

Previously we observed strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B6 during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B6 excretion. Possible causes of decreased levels of vitamin B6 are discussed.

Changes of glucose metabolism and skin-collagen neogenesis in vitamin B6 deficiency. Biofactors. 2005;23(2):59-67.

The mechanism of pellagrous changes in skin caused by a deficiency of vitamin B6 was studied in respect to neogenesis of proline in skin collagen and glucose metabolism. In vitamin B6 deficiency the insulin/glucagon coefficient in serum decreased significantly from 3.02 to 2.32, indicating a metabolic change towards gluconeogenesis. A deficiency of vitamin B6 caused a decrease in the levels of vitamin B6-dependent enzymes, such as ornithine aminotransferase, alanine aminotransferase, and aspartate aminotransferase, which also contribute to gluconeogenesis. Because the conversion of ornithine to proline via pyrroline-5-carboxylate was suppressed due to the decrease in ornithine aminotransferase activity, the amount of proline in the skin collagen fraction also decreased significantly in vitamin B6-deficient rats compared with the pair-fed control. These results suggest that the pellagrous lesions in vitamin B6-deficiency are caused by an impaired synthesis of proline from ornithine, which results in the suppression of collagen neogenesis in the skin.

Homocysteine, vitamin B6 and the risk of recurrent venous thromboembolism. Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):342-4.

Hyperhomocysteinemia (HHC) is an independent risk factor for cardiovascular disease, and even mildly to moderately elevated homocysteine levels have been associated with a heightened risk for a first and recurrent venous thromboembolism (VTE). Within the frame of a large prospective cohort study (Austrian Study on Recurrent Venous Thromboembolism), we assessed the impact of HHC on the risk of recurrence among 602 patients with a first unprovoked VTE. HHC was an independent risk factor of recurrence conferring a relative risk of 1.5 (95th% CI 1.0-2.4). HHC is caused either by genetic defects and/or by a deficiency of the vitamins (B12, B6 and folic acid) involved in the homocysteine metabolism. Low vitamin B6 levels are associated with an increased risk of a first venous thrombosis.We currently investigate whether or not low plasma levels of PLP are associated with a heightened risk for recurrent VTE.